Ying Qing Chen

All Publications

• Use of Coronary Artery Bypass Graft Surgery and Percutaneous Coronary Intervention and Associated Outcomes in the ISCHEMIA Trial. American heart journal White, H. D., O'Brien, S. M., Boden, W. E., Fremes, S. E., Bangalore, S., Reynolds, H. R., Stone, G. W., Ali, Z. A., Parakh, N., Lopez-Sendon, J. L., Wang, Y., Chen, Y. Q., Mark, D. B., Chaitman, B. R., Spertus, J. A., Maron, D. J., Hochman, J. S., ISCHEMIA Research Group 2025

  Abstract

  BACKGROUND: In the ISCHEMIA Trial, 5179 patients with stable coronary disease were randomized to initial invasive or conservative management.METHODS: PCI was recommended with a SYNTAX score 0-22 (low) and CABG with a SYNTAX score ≥33 (high). Either could be recommended for intermediate scores. The composite primary outcome was cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. There were two cohorts in this analysis. The descriptive cohort included patients who underwent CABG or PCI within 180 days of randomization and had no primary outcome before revascularization. The comparative cohort excluded participants with prior CABG, single vessel disease, SYNTAX score ≥ 45, and without core laboratory assessment. We focused on the intermediate (23-32) SYNTAX comparative group for which either CABG or PCI could be recommended.RESULTS: For 1935 patients in the descriptive cohort (485 CABG, 1450 PCI), the SYNTAX score was 27.3 ± 11.0 in the CABG group and 15.3 ± 8.6 in the PCI group, p<0.0001. Most patients with low SYNTAX scores underwent PCI (87.1%), while most with high SYNTAX scores underwent CABG (72.6%). For the 1203 patients (385 CABG, 818 PCI) in the entire comparative cohort, the adjusted 4-year primary event rate was 14.5% for CABG and 13.2% for PCI (difference 1.3%, 95% CI, -4.9% to 7.7%). For the 346 patients (163 CABG, 183 PCI) in the intermediate SYNTAX group, the adjusted 4-year primary event rate was 10.6% for CABG and 18.3% for PCI (difference -7.6%, 95% CI, -16.1% to 0.9%).CONCLUSIONS: Selection of revascularization method resulted in more PCI in the low SYNTAX group and more CABG in the high SYNTAX group. There was no statistical evidence of a difference between PCI and CABG in the intermediate SYNTAX group but the CIs are broad, reflecting uncertainty.CLINICAL TRIALS:GOV IDENTIFIER: NCT01471522; https://clinicaltrials.gov/ct2/show/NCT01471522.

  View details for DOI 10.1016/j.ahj.2025.05.009

  View details for PubMedID 40404111

• Absorbing Markov chain model of PrEP drug adherence to estimate adherence decay rate and probability distribution in clinical trials JOURNAL OF THEORETICAL BIOLOGY Dale, R., He, H., Chen, Y. 2025; 604: 112086

  Abstract

  Pre-exposure prophylaxis (PrEP) is increasingly used to prevent the transmission of H.I.V. in at-risk populations. However, PrEP users may discontinue use of the medicine due to side effects, lower perceived risk, or other reasons. The usage metrics of 594 individuals was tracked over 350 days using the Wisepill electronic monitoring system. We model the PrEP drug adherence level using an absorbing Markov chain with a unique absorbing state. The transition matrix T obtained from the Wisepill data will have a trivial eigenvector (eigendistribution) associated with the first (i.e., largest) eigenvalue 1. The 2nd eigenvalue(s) then become important in determining the asymptotic behavior of the Markov chain, dictating how fast the Markov chain decays to the absorbing state. Under a fairly general assumption, we prove that the second positive eigenvalue is unique and the corresponding eigenvector will have nonnegative entries with exceptions at absorbing states. In addition, we define the asymptotic half life of the absorbing Markov chain directly from the 2nd eigenvalue. We then determine the 2nd eigenvalue of T and the asymptotic half life of the Markov chain, which turns out to be very close to the real half life of the Markov chain. Finally, we interpret the 2nd eigenvector as the relative probability distribution of X∞ with respect to the decay rate of the 2nd eigenvalue. By applying these methods to the Wisepill data, we estimate the half-life of population adherence to be 46 weeks. The bi-weekly decay rate observed in these data from 90 to 100 % adherence is 3 %. This work produces an estimate at which adherence falls over time, given no external intervention is applied. These results suggest an eigenvector-based approach to estimate adherence trends, as well as the timing of interventions to improve adherence.

  View details for DOI 10.1016/j.jtbi.2025.112086

  View details for Web of Science ID 001448079100001

  View details for PubMedID 40086122

  View details for PubMedCentralID PMC12037977

• On Data-Enriched Logistic Regression MATHEMATICS Zheng, C., Dasgupta, S., Xie, Y., Haris, A., Chen, Y. 2025; 13 (3)

  View details for DOI 10.3390/math13030441

  View details for Web of Science ID 001418671500001

• Semiparametric Trend Analysis for Stratified Recurrent Gap Times Under Weak Comparability Constraint. Statistics in biosciences Liu, P., Huang, Y., Chan, K. C., Chen, Y. Q. 2023; 15 (2): 455-474

  Abstract

  Recurrent event data are frequently encountered in many longitudinal studies where each individual may experience more than one event. Wang and Chen (Biometrics 56(3):789-794, 2000) proposed a comparability constraint to estimate the time trend for the gap times, where the gap time pairs that satisfy the constraint have the same conditional distribution. However, the comparable paired gap times are also independent. Therefore, the comparable gap time pairs will be subject to a stronger constraint than needed for the estimation. Thus their procedure is subject to information loss. Under the accelerated failure time model, we propose a new comparability constraint that can overcome the drawback mentioned above. The gap time pairs being selected by the proposed comparability constraint will still have the same distribution, but they do not need to be independent of each other. We showed that the proposed comparability constraint will utilize more gap time data pairs than the strong comparability. And we showed via various simulation studies that the variance will be smaller than Wang and Chen's (2000) estimator. We apply the proposed method to the HIV Prevention Trial Network 052 study.

  View details for DOI 10.1007/s12561-023-09376-8

  View details for PubMedID 39512240

  View details for PubMedCentralID PMC11542620

• Semiparametric Trend Analysis for Stratified Recurrent Gap Times Under Weak Comparability Constraint STATISTICS IN BIOSCIENCES Liu, P., Huang, Y., Chan, K., Chen, Y. 2023

  View details for DOI 10.1007/s12561-023-09376-8

  View details for Web of Science ID 000999954100002

• Population-Level Effectiveness of an Inactivated Whole-Virion COVID-19 Vaccine: A Test Negative Case-Control Study in the Dominican Republic. Open forum infectious diseases Pérez-Then, E., Miric, M., Qian, H. Z., Chen, Y. Q., Wang, Y., Vallejo, V., Quezada, W., Flaquer, M., Olivo, J., Castillo, J., García, N., Calderón, K., Cueto, S., Veras, B., Russo, M., Jiménez, I., Guzmán, S., Garabito, L., Cueto, E., Colombo, F., Taveras, D., Torres, D., Baez, J., Yunen, J., Koenig, E., Pérez, E., López, O., Severino Medina, F. E., Wang, X., Shao, Y., Vermund, S. H. 2023; 10 (3): ofad075

  Abstract

  A continuing nationwide vaccination campaign began in the Dominican Republic on February 16, 2021 to prevent severe consequences of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Estimates of vaccine effectiveness under real-world conditions are needed to support policy decision making and inform further vaccine selection.We conducted a test-negative case-control study to assess the real-world effectiveness of nationwide coronavirus disease 2019 (COVID-19) vaccination program using an inactivated vaccine (CoronaVac) on preventing symptomatic SARS-CoV-2 infections and hospitalizations from August to November 2021 in the Dominican Republic. Participants were recruited from 10 hospitals in 5 provinces to estimate the effectiveness of full immunization (≥14 days after receipt of the second dose) and partial immunization (otherwise with at least 1 dose ≥14 days after receipt of the first dose).Of 1078 adult participants seeking medical care for COVID-19-related symptoms, 395 (36.6%) had positive polymerase chain reaction (PCR) tests for SARS-CoV-2; 142 (13.2%) were hospitalized during 15 days of follow up, including 91 (23%) among 395 PCR-positive and 51 (7.5%) among 683 PCR-negative participants. Full vaccination was associated with 31% lower odds of symptomatic infection (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.93) and partial vaccination was associated with 49% lower odds (OR, 0.51; CI, 0.30-0.86). Among 395 PCR-positive participants, full vaccination reduced the odds of COVID-19-related hospitalization by 85% (OR, 0.15; 95% CI, 0.08-0.25) and partial vaccination reduced it by 75% (OR, 0.25; 95% CI, 0.08-0.80); full vaccination was associated with reduced use of assisted ventilation by 73% (OR, 0.27; 95% CI, 0.15-0.49).Given the ancestral and delta viral variants circulating during this study period, our results suggest that the inactivated COVID-19 vaccine offered moderate protection against symptomatic SARS-CoV-2 infections and high protection against COVID-19-related hospitalizations and assisted ventilation. This is reassuring given that, as of August 2022, an estimated 2.6 billion inactivated CoronaVac vaccine doses had been administered worldwide. This vaccine will become a basis for developing multivalent vaccine against the currently circulating omicron variant.

  View details for DOI 10.1093/ofid/ofad075

  View details for PubMedID 36998630

  View details for PubMedCentralID PMC10043129

• On a simple estimation of the proportional odds model under right truncation. Lifetime data analysis Liu, P., Chan, K. C., Chen, Y. Q. 2023

  Abstract

  Retrospective sampling can be useful in epidemiological research for its convenience to explore an etiological association. One particular retrospective sampling is that disease outcomes of the time-to-event type are collected subject to right truncation, along with other covariates of interest. For regression analysis of the right-truncated time-to-event data, the so-called proportional reverse-time hazards model has been proposed, but the interpretation of its regression parameters tends to be cumbersome, which has greatly hampered its application in practice. In this paper, we instead consider the proportional odds model, an appealing alternative to the popular proportional hazards model. Under the proportional odds model, there is an embedded relationship between the reverse-time hazard function and the usual hazard function. Building on this relationship, we provide a simple procedure to estimate the regression parameters in the proportional odds model for the right truncated data. Weighted estimations are also studied.

  View details for DOI 10.1007/s10985-022-09584-2

  View details for PubMedID 36602639

• Pregnancy rates and clinical outcomes among women living with HIV enrolled in HPTN 052 AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV Zangeneh, S. Z., Wilson, E. A., Ahluwalia, S., Donnell, D. J., Chen, Y. Q., Grinsztejn, B., Melo, M. G., Godbole, S. V., Hosseinipour, M. C., Taha, T., Kumwenda, J., McCauley, M., Cohen, M. S., Nielsen-Saines, K. 2022: 1-9

  Abstract

  HPTN 052 was a multi-country clinical trial of cART for preventing heterosexual HIV-1 transmission. The study allowed participation of pregnant women and provided access to cART and contraceptives. We explored associations between pregnancy and clinical measures of HIV disease stage and progression. Of 869 women followed for 5.70 (SD = 1.62) years, 94.7% were married/cohabitating, 96% initiated cART, and 76.3% had >2 past pregnancies. Of 337 women who experienced pregnancy, 89.3% were from countries with lower contraceptive coverage, 56.1% first started cART with PI-based regimens and 57.6% were 25-34 years old. Mean cART duration and condom use were similar among pregnant and nonpregnant individuals. Adjusting for confounders, viral load suppression (VLS) was not (aHR(CI) = 0.82(0.61, 1.08)) and CD4 was slightly associated with decreased rates of first pregnancy over time (aHR(CI) = 0.9(0.84, 0.95)); baseline VLS was associated with increased (aRR(CI) = 2.48(1.71, 3.59)) and baseline CD4 was slightly associated with decreased number of pregnancies (aRR(CI) = 0.9(0.85,0.96)) over study duration. Partner seroconversion was univariably associated with higher rates of first pregnancy (HR(CI) = 2.02(1.32,3.07)). Despite a background of higher maternal morbidity and mortality rates, our findings suggest that becoming pregnant does not pose a threat to maternal health in women with HIV when there is access to medical care and antiretroviral treatment.

  View details for DOI 10.1080/09540121.2022.2141187

  View details for Web of Science ID 000899520400001

  View details for PubMedID 36524872

• Sexual behavior and medication adherence in men who have sex with men participating in a pre-exposure prophylaxis study of combinations of Maraviroc, Tenofovir Disoproxil Fumarate and/or Emtricitabine (HPTN 069/ACTG 5305) AIDS AND BEHAVIOR Mayer, K. H., Yuhas, K., Amico, K., Wilkin, T., Landovitz, R. J., Richardson, P., Marzinke, M. A., Eshleman, S. H., Cottle, L. M., Marcus, C., Chege, W., Rinehart, A. R., Rooney, J. F., Andrew, P., Salata, R. A., Magnus, M., Farley, J. E., Liu, A. Y., Frank, I., Ho, K., Santana, J., Stekler, J. D., Chen, Y. Q., McCauley, M., Gulick, R. M. 2022

  Abstract

  HPTN 069/ACTG 5305 was designed to evaluate potential new PrEP regimens that included maraviroc, tenofovir disoproxil fumarate, and/or emtricitabine. The current analyses assessed antiretroviral (ARV) plasma concentrations in relation to sexual behavior in 224 cisgender men who have sex with men and 2 transgender women at risk for HIV. Poisson generalized estimating equations (GEE) regression were used to test for associations between self-reported sexual behavior, sociodemographic, behavioral variables, and study drug levels The median (IQR) age was 30 [25, 37] years old; 48.2% had completed college; 27.4% were Black and 21.7% Latino. At weeks 24 and 48, one third of participants reported condomless anal sex (CAS) in the prior month with more than one partner. CAS was associated with daily ARV drug use (χ2 = 12.64, p = 0.002). Older individuals and those with greater education were more likely to ingest ARV drugs daily (χ2 = 9.36, p = 0.009 and χ2 = 8.63, p = 0.013, respectively), while neither race nor ethnicity was associated with daily ARV drug use. Participants who reported recent condomless anal sex and/or advanced education had higher rates of daily ARV drug use. These data support the need for ongoing adherence counseling in clinical trials of new PrEP modalities.

  View details for DOI 10.1007/s10461-022-03736-z

  View details for Web of Science ID 000809325200006

  View details for PubMedID 35687192

• A Surrogate Measure for Time-Varying Biomarkers in Randomized Clinical Trials. Mathematics (Basel, Switzerland) Zhuang, R., Xia, F., Wang, Y., Chen, Y. Q. 2022; 10 (4)

  Abstract

  Clinical trials with rare or distant outcomes are usually designed to be large in size and long term. The resource-demand and time-consuming characteristics limit the feasibility and efficiency of the studies. There are motivations to replace rare or distal clinical endpoints by reliable surrogate markers, which could be earlier and easier to collect. However, statistical challenges still exist to evaluate and rank potential surrogate markers. In this paper, we define a generalized proportion of treatment effect for survival settings. The measure's definition and estimation do not rely on any model assumption. It is equipped with a consistent and asymptotically normal non-parametric estimator. Under proper conditions, the measure reflects the proportion of average treatment effect mediated by the surrogate marker among the group that would survive to mark the measurement time under both intervention and control arms.

  View details for DOI 10.3390/math10040584

  View details for PubMedID 39512426

  View details for PubMedCentralID PMC11542621

• A surrogate measure for time-varying biomarkers in randomized clinical trials Mathematics Y, Z., F, X., Y, W., Y. Q., C. 2022; 10 (4): 584

  View details for DOI 10.3390/math10040584

• Uptake of antiretroviral treatment and viral suppression among men who have sex with men and transgender women in sub-Saharan Africa in an observational cohort study: HPTN 075 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Palumbo, P. J., Zhang, Y., Clarke, W., Breaud, A., Sivay, M., Cummings, V., Hamilton, E. L., Guo, X., Ogendo, A., Kayange, N., Panchia, R., Dominguez, K., Chen, Y. Q., Sandfort, T. M., Eshleman, S. H. 2021; 104: 465–70

  Abstract

  HPTN 075 enrolled men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa. Persons in HIV care or on antiretroviral treatment (ART) were not eligible to enroll. We evaluated antiretroviral (ARV) drug use, viral suppression, and drug resistance in this cohort over a 12-month follow-up period.Assessments included 64 participants with HIV (39 MSM, 24 TGW, and one gender not specified). ARV drugs were detected using a qualitative assay. Viral load (VL) and drug resistance testing were performed using commercial assays.Over 12 months, the proportion of participants using ARV drugs increased from 28.1% to 59.4% and the proportion with VLs <400 copies/mL increased from 21.9% to 57.8%. The rate of ART failure (detection of drugs without viral suppression) was similar at screening and 12 months (12.0% and 11.1%, respectively) and was similar among MSM and TGW. Two participants developed HIV drug resistance during follow-up.Over 12 months, ARV drug use in the cohort more than doubled and viral suppression increased nearly threefold without a significant increase in ART failure or drug resistance. These results suggest that ART can be successfully scaled up for HIV prevention and treatment in this high-risk population.

  View details for DOI 10.1016/j.ijid.2020.12.085

  View details for Web of Science ID 000632937400024

  View details for PubMedID 33440260

  View details for PubMedCentralID PMC8091139

• Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Zhang, Y., Wymant, C., Laeyendecker, O., Grabowski, M. K., Hall, M., Hudelson, S., Piwowar-Manning, E., McCauley, M., Gamble, T., Hosseinipour, M. C., Kumarasamy, N., Hakim, J. G., Kumwenda, J., Mills, L. A., Santos, B. R., Grinsztejn, B., Pilotto, J. H., Chariyalertsak, S., Makhema, J., Chen, Y. Q., Cohen, M. S., Fraser, C., Eshleman, S. H. 2021; 72 (1): 30-37

  Abstract

  Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction.Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env).Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction.We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

  View details for DOI 10.1093/cid/ciz1247

  View details for PubMedID 31922537

  View details for PubMedCentralID PMC7823077

• Measuring Surrogacy in Clinical Research With an Application to Studying Surrogate Markers for HIV Treatment-as-Prevention STATISTICS IN BIOSCIENCES Zhuang, R., Chen, Y. 2020; 12 (3): 295–323

  Abstract

  In clinical research, validated surrogate markers are highly desirable in study design, monitoring, and analysis, as they do not only reduce the required sample size and follow-up duration, but also facilitate scientific discoveries. However, challenges exist to identify a reliable marker. One particular statistical challenge arises on how to measure and rank the surrogacy of potential markers quantitatively. We review the main statistical methods for evaluating surrogate markers. In addition, we suggest a new measure, the so-called "population surrogacy fraction of treatment effect," or simply the p-measure, in the setting of clinical trials. The p-measure carries an appealing population impact interpretation and supplements the existing statistical measures of surrogacy by providing "absolute" information. We apply the new measure along with other prominent measures to the HIV Prevention Trial Network 052 Study, a landmark trial for HIV/AIDS treatment-as-prevention.

  View details for DOI 10.1007/s12561-019-09244-4

  View details for Web of Science ID 000585702200004

  View details for PubMedID 33737982

  View details for PubMedCentralID PMC7962622

• Introduction to Special Issue on 'Statistical Methods for HIV/AIDS Research' STATISTICS IN BIOSCIENCES Chen, Y. 2020; 12 (3): 263–66

  View details for DOI 10.1007/s12561-020-09296-x

  View details for Web of Science ID 000579725100001

  View details for PubMedID 33101525

  View details for PubMedCentralID PMC7569197

• The feasibility of recruiting and retaining men who have sex with men and transgender women in a multinational prospective HIV prevention research cohort study in sub-Saharan Africa (HPTN 075) JOURNAL OF THE INTERNATIONAL AIDS SOCIETY Sandfort, T. M., Hamilton, E., Marais, A., Guo, X., Sugarman, J., Chen, Y. Q., Cummings, V., Dadabhai, S., Dominguez, K., Panchia, R., Schnabel, D., Zulu, F., Reynolds, D., Radebe, O., Mbeda, C., Kamba, D., Kanyemba, B., Ogendo, A., Stirratt, M., Chege, W., Lucas, J., Fawzy, M., McKinstry, L. A., Eshleman, S. H. 2020; 23: e25600

  Abstract

  Men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA) are profoundly affected by HIV with high HIV prevalence and incidence. This population also faces strong social stigma and legal barriers, potentially impeding participation in research. To date, few multi-country longitudinal HIV research studies with MSM/TGW have been conducted in SSA. Primary objective of the HIV Prevention Trials Network (HPTN) 075 study was to assess feasibility of recruiting and retaining a multinational prospective cohort of MSM/TGW in SSA for HIV prevention research.HPTN 075, conducted from 2015 to 2017, was designed to enroll 400 MSM/TGW at four sites in SSA (100 per site: Kisumu, Kenya; Blantyre, Malawi; Cape Town, South Africa; and Soweto, South Africa). The number of HIV-positive persons was capped at 20 per site; HIV-positive persons already in care were excluded from participation. The one-year study included five biobehavioural assessments. Community-based input and risk mitigation protocols were included in study design and conduct.Of 624 persons screened, 401 were enrolled. One in five participants was classified as transgender. Main reasons for ineligibility included: (a) being HIV positive after the cap was reached (29.6%); (b) not reporting anal intercourse with a man in the preceding three months (20.6%); and (c) being HIV positive and already in care (17.5%). Five (1.2%) participants died during the study (unrelated to study participation). 92.9% of the eligible participants (368/396) completed the final study visit and 86.1% participated in all visits. The main, overlapping reasons for early termination included being (a) unable to adhere to the visit schedule, predominantly because of relocation (46.4%), and (b) unable to contact the participant (32.1%). Participants reported strong motivation to participate and few participation barriers. Four participants reported social harms (loss of confidentiality and sexual harassment by study staff) that were successfully addressed.HPTN 075 successfully enrolled a multinational sample of MSM/TGW in SSA in a prospective HIV prevention research study with a high retention rate and few documented social harms. This supports the feasibility of conducting large-scale research trials in this population to address its urgent, unmet HIV prevention needs.

  View details for DOI 10.1002/jia2.25600

  View details for Web of Science ID 000576983100009

  View details for PubMedID 33000911

  View details for PubMedCentralID PMC7527761

• Persistence of oral pre-exposure prophylaxis (PrEP) among adolescent girls and young women initiating PrEP for HIV prevention in Kenya AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV Tapsoba, J., Zangeneh, S. Z., Appelmans, E., Pasalar, S., Mori, K., Peng, L., Tao, J., Drain, P., Okomo, G., Bii, S., Mukabi, J., Zobrist, S., Brady, M., Obanda, R., Madiang, D., Cover, J., Duerr, A., Chen, Y., Obong'o, C. 2020: 1–9

  Abstract

  The Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) Initiative aims to reduce HIV infections among adolescent girls and young women (AGYW) in Africa. Oral pre-exposure prophylaxis (PrEP) is offered through DREAMS in Kenya to eligible AGYW in high burden counties including Kisumu and Homa Bay. This study examines PrEP persistence among AGYW in high burden community-based PrEP delivery settings. We evaluated PrEP persistence among AGYW in the DREAMS PrEP program in Kisumu and Homa Bay using survival analysis and programmatic PrEP refill data collected between March through December 2017. Among 1,259 AGYW who initiated PrEP during the study period, the median persistence time in the program was 56 days (95% CI: 49-58 days) and the proportion who persisted 3 months later was 37% (95% CI: 34-40%). Persistence varied by county (p < 0.001), age at PrEP initiation (p = 0.002), marital status (p = 0.008), transactional sex (p = 0.002), gender-based violence (GBV) experience (p = 0.009) and current school attendance (p = 0.001) at DREAMS enrollment. Persistence did not vary with orphan status, food insecurity, condom use, age at first sexual encounter or engagement in age-disparate sex at DREAMS enrollment. Targeted strategies are needed to improve AGYW retention in the PrEP program.

  View details for DOI 10.1080/09540121.2020.1822505

  View details for Web of Science ID 000571280600001

  View details for PubMedID 32951437

  View details for PubMedCentralID PMC7981281

• Trial designs for evaluating combination HIV prevention approaches HIV RESEARCH & CLINICAL PRACTICE Chen, Y., Peng, L., Wang, Y., Appelmans, E., Dasgupta, S., Fleming, T. R. 2020; 21 (2-3): 72–82

  Abstract

  Combination HIV prevention approaches that include both biomedical and non-biomedical interventions often hold greater promise to improve health outcomes and reduce the risk of HIV transmission.Evaluate the relative properties of four leading candidate trial designs - 'single-factor', 'multi-arm', 'all-in-one', and 'factorial' designs - for assessing individual and/or combination prevention intervention approaches.Monte-Carlo simulations are conducted, assuming a putative combination approach could choose its components from two candidate biomedical interventions, i.e. Treatment-as-Prevention (TasP) and Pre-exposure Prophylaxis (PrEP), and three candidate behavioral interventions, i.e. linkage-to-care, counseling, and use of condoms. Various scenarios for individual components' effect sizes, their possible interaction, and the sample size based on real clinical studies are considered.The all-in-one and factorial designs used to assess a combination approach and the multi-arm design used to assess multiple individual components are consistently more powerful than single-factor designs. The all-in-one design is powerful when the individual components are effective without negative interaction, while the factorial design is more consistently powerful across a broad array of settings.The multi-arm design is useful for evaluating single factor regimens, while the all-in-one and factorial designs are sensitive in assessing the overall efficacy when there is interest in combining individual component regimens anticipated to have complementary mechanisms. The factorial design is a preferred approach when assessing combination regimens due to its favorable power properties and since it is the only design providing direct insights about the contribution of individual components to the combination approach's overall efficacy and about potential interactions.

  View details for DOI 10.1080/25787489.2020.1798083

  View details for Web of Science ID 000555063900001

  View details for PubMedID 32698705

  View details for PubMedCentralID PMC7608072

• Healthcare-related stigma among men who have sex with men and transgender women in sub-Saharan Africa participating in HIV Prevention Trials Network (HPTN) 075 study AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV Mbeda, C., Ogendo, A., Lando, R., Schnabel, D., Gust, D. A., Guo, X., Akelo, V., Dominguez, K., Panchia, R., Mbilizi, Y., Chen, Y., Chege, W., Sandfort, T., HPTN 075 Protocol Team 2020; 32 (8): 1052–60

  Abstract

  ABSTRACT The inability to access health services when needed is a critical barrier to HIV prevention, treatment and care among men who have sex with men (MSM) and transgender women (TGW). Using data collected in HPTN 075, we explored factors associated with any experienced healthcare-related stigma. HPTN 075 was a cohort study to assess the feasibility of recruiting and retaining MSM and TGW in clinical trials in sub-Saharan Africa. Of 401 MSM and TGW enrolled at four sites (Kisumu, Kenya; Blantyre, Malawi; Cape Town, Soweto, South Africa) 397 contributed to the analysis (79.9% cis-gender and 20.1% TGW). Of these, (45.3%; 180/397) reported one or more of healthcare-related stigma experiences. Most frequently reported experiences included fear to seek healthcare services (36.3%) and avoiding seeking such services because of the discovery of MSM status (29.2%). Few men and TGW (2.5%) reported having been denied health services because of having sex with men. In multivariable analysis, more participants in Soweto [adjusted odds ratio (AOR) = 2.60] and fewer participants in Blantyre (AOR = 0.27) reported any healthcare-related stigma experiences, in comparison to participants in Kisumu. MSM and TGW that did not have a supportive gay community to rely on were more likely to report any healthcare-related stigma experiences (AOR = 1.46), whereas MSM and TGW who reported high social support and who never had engaged in transactional sex were less likely to report such experiences (AOR = 0.76 and AOR = 0.43, respectively). Our results suggest that encouraging support groups for MSM and TGW as well as training and sensitizing healthcare staff, and the general community, on MSM and TGW health issues and cultural competence may reduce stigma, improve access to healthcare, which could ultimately reduce HIV transmission.

  View details for DOI 10.1080/09540121.2020.1776824

  View details for Web of Science ID 000542822200001

  View details for PubMedID 32500722

  View details for PubMedCentralID PMC7368806

• On a Statistical Transmission Model in Analysis of the Early Phase of COVID-19 Outbreak STATISTICS IN BIOSCIENCES Zhu, Y., Chen, Y. 2021; 13 (1): 1–17

  Abstract

  Since December 2019, a disease caused by a novel strain of coronavirus (COVID-19) had infected many people and the cumulative confirmed cases have reached almost 180,000 as of 17, March 2020. The COVID-19 outbreak was believed to have emerged from a seafood market in Wuhan, a metropolis city of more than 11 million population in Hubei province, China. We introduced a statistical disease transmission model using case symptom onset data to estimate the transmissibility of the early-phase outbreak in China, and provided sensitivity analyses with various assumptions of disease natural history of the COVID-19. We fitted the transmission model to several publicly available sources of the outbreak data until 11, February 2020, and estimated lock down intervention efficacy of Wuhan city. The estimated R 0 was between 2.7 and 4.2 from plausible distribution assumptions of the incubation period and relative infectivity over the infectious period. 95% confidence interval of R 0 were also reported. Potential issues such as data quality concerns and comparison of different modelling approaches were discussed.

  View details for DOI 10.1007/s12561-020-09277-0

  View details for Web of Science ID 000523054500001

  View details for PubMedID 32292527

  View details for PubMedCentralID PMC7113380

• A regularized estimation approach for case-cohort periodic follow-up studies with an application to HIV vaccine trials BIOMETRICAL JOURNAL Zhao, H., Wu, Q., Gilbert, P. B., Chen, Y. Q., Sun, J. 2020; 62 (5): 1176–91

  Abstract

  This paper discusses regression analysis of the failure time data arising from case-cohort periodic follow-up studies, and one feature of such data, which makes their analysis much more difficult, is that they are usually interval-censored rather than right-censored. Although some methods have been developed for general failure time data, there does not seem to exist an established procedure for the situation considered here. To address the problem, we present a semiparametric regularized procedure and develop a simple algorithm for the implementation of the proposed method. In addition, unlike some existing procedures for similar situations, the proposed procedure is shown to have the oracle property, and an extensive simulation is conducted and it suggests that the presented approach seems to work well for practical situations. The method is applied to an HIV vaccine trial that motivated this study.

  View details for DOI 10.1002/bimj.201900180

  View details for Web of Science ID 000514617400001

  View details for PubMedID 32080888

  View details for PubMedCentralID PMC7768636

• Methods for generalized change-point models: with applications to human immunodeficiency virus surveillance and diabetes data STATISTICS IN MEDICINE Tapsoba, J., Wang, C., Zangeneh, S., Chen, Y. 2020; 39 (8): 1167–82

  Abstract

  In many epidemiological and biomedical studies, the association between a response variable and some covariates of interest may change at one or several thresholds of the covariates. Change-point models are suitable for investigating the relationship between the response and covariates in such situations. We present change-point models, with at least one unknown change-point occurring with respect to some covariates of a generalized linear model for independent or correlated data. We develop methods for the estimation of the model parameters and investigate their finite-sample performances in simulations. We apply the proposed methods to examine the trends in the reported estimates of the annual percentage of new human immunodeficiency virus (HIV) diagnoses linked to HIV-related medical care within 3 months after diagnosis using HIV surveillance data from the HIV prevention trial network 065 study. We also apply our methods to a dataset from the Pima Indian diabetes study to examine the effects of age and body mass index on the risk of being diagnosed with type 2 diabetes.

  View details for DOI 10.1002/sim.8469

  View details for Web of Science ID 000510844600001

  View details for PubMedID 31997385

  View details for PubMedCentralID PMC7260994

• Adjusted time-varying population attributable hazard in case-control studies STATISTICAL METHODS IN MEDICAL RESEARCH Zhao, W., Zheng, J., Chen, Y., Hsu, L. 2020; 29 (1): 243–57

  Abstract

  Population attributable fraction is a widely used measure for quantifying the disease burden associated with a modifiable exposure of interest at the population level. It has been extended to a time-varying measure, population attributable hazard function, to provide additional information on when and how the exposure's impact varies over time. However, like the classic population attributable fraction, the population attributable hazard is generally biased if confounders are present. In this article, we provide a natural definition of adjusted population attributable hazard to take into account the effects of confounders, and its alternative that is identifiable from case-control studies under the rare disease assumption. We propose a novel estimator, which combines the odds ratio estimator from logistic regression model, and the conditional density function estimator of the exposure and confounding variables distribution given the failure times of cases or the current times of controls from a kernel smoother. We show that the proposed estimators are consistent and asymptotically normal with variance that can be estimated empirically from the data. Simulation studies demonstrate that the proposed estimators perform well in finite sample sizes. Finally, we illustrate the method by an analysis of a case-control study of colorectal cancer. Supplementary materials for this article are available online.

  View details for DOI 10.1177/0962280219831725

  View details for Web of Science ID 000508982300017

  View details for PubMedID 30799773

  View details for PubMedCentralID PMC7261419

• On a Shape-Invariant Hazard Regression Model with application to an HIV Prevention Study of Mother-to-Child Transmission STATISTICS IN BIOSCIENCES Zheng, C., Chen, Y. 2020; 12 (3): 340–52

  Abstract

  In survival analysis, Cox model is widely used for most clinical trial data. Alternatives include the additive hazard model, the accelerated failure time (AFT) model and a more general transformation model. All these models assume that the effects for all covariates are on the same scale. However, it is possible that for different covariates, the effects are on different scales. In this paper, we propose a shape-invariant hazard regression model that allows us to estimate the multiplicative treatment effect with adjustment of covariates that have non-multiplicative effects. We propose moment-based inference procedures for the regression parameters. We also discuss the risk prediction and the goodness of fit test for our proposed model. Numerical studies show good finite sample performance of our proposed estimator. We applied our method to the HIVNET 012 study, a milestone trial of single-dose nevirapine in prevention of mother-to-child transmission of HIV. From the HIVNET 012 data analysis, single-dose nevirapine treatment is shown to improve 18-month infant survival significantly with appropriate adjustment of the maternal CD4 counts and the virus load.

  View details for DOI 10.1007/s12561-019-09260-4

  View details for Web of Science ID 000491530600002

  View details for PubMedID 33312265

  View details for PubMedCentralID PMC7730855